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In depth view of Cohort Study

In depth view of Cohort Study

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  • By definition, such cases are not free of a specified disease, as in the case of a conventional cohort study (but are free of the ‘outcome of interest’).
  • If the follow-up of fixed cohorts suffers from losses to follow-up incidence rates can still be measured directly and used to estimate average risks and incidence times. Accrue : periodic accumulated over time
  • if all workers at the factory had some degree of exposure, we would need to select a comparison group from another population, possibly another type of factory, to ensure that the comparison group only differed in terms of their exposure and not in terms of other factors.
  • In this case, outcome events are preferably described by rates, that represent the number of outcome events divided by the cumulated duration of event-free follow-up periods of all cohort members at risk.
  • Relative Risk(RR ) = Incidence of disease(or death) among exposed / Incidence of disease(or death) among non-exposed. Relative Risk(RR)= { A/(A+B)}/ { C/(C+D)}
  • Defined as the ratio of the incidence of disease in the exposed group (expressed as I e ) divided by the corresponding incidence of disease in the non exposed group (I o )
  • This is an important study and follow-up of participants is still under way. Results for 50 years of follow-up were published recently in the British Medical Journal (Doll et al. 2004).
  • the estimation of level of exposure to tobacco by counting the number of cigarettes smoked per day may not be appropriate. For instance, the duration of smoking, inhalation practices and age when started to smoke might have been different Since mortality depends on age and the distribution of subjects by age group is different between the smokers and non-smokers, the effect of age on mortality has to be adjusted for when making comparison on lung cancer mortality between these two groups. A commonly used method to adjust for the age is direct standardization between the men and women. Unless the effects of these features of smoking are taken into account, one cannot conclude that low to moderate smoking has a higher effect in men than in women.
  • In epidemiological cohort studies the standard model for analyzing such data is the Poisson model which is a statistical model of the disease rates. Basically the Poisson model assumes that the number of events di in each category i (combination of age category j and the kth combination of exposure variables) follows a Poisson distribution with parameter niλi. The standard (multiplicative) model would then assume that ln( λ i) = α j + β k A comprehensive account of Poisson modeling is given by Breslow and Day (1987, Chap. 4). An alternative way of analysing event history data (another denomination of cohort data focussed on events), is by using Cox’ proportional hazard model. This model acknowledges that the categorisation of continuous data always implies a loss of information and therefore a loss in statistical power.Moreover, there is no need to explicitly estimate the effects of nuisance parameters if it can be avoided. The first step in proportional hazard model is the choice of one of the time variables considered. This basic time variable can either be age as was implicit at the beginning of this chapter, but in some settings, this variable can be the calendar time or even the time since the beginning of follow-up. Once this special time variable has been fixed, its effects are estimated nonparametrically. The key idea of Cox’s regression is that no information is lost when considering only the time points ti at which an event of interest occurs. At each such time point a “risk set” is set up including all members of the cohort contributing person-time (at risk and under observation) at this time point. If one wants to use a Cox model, the first step is thus to identify all risk sets. Then, one must obtain the value at
  • Once investigators assemble the study cohorts, they are free to study more than one outcome, provided that the study subjects are free of each outcome of interest when the study begins. For the smoking and kidney transplant failure example, once cohorts of smokers and non-smokers are identified, investigators could also study whether smoking was associated with the development of kidney or bladder cancer, provided they exclude individuals who have evidence of these cancers at the beginning of the study. One of the largest cohort studies even conducted was the Nurses Health Study, which recruited 127,000 nurses between the ages of 30 and 55. The nurses completed questionnaires every 2 years that queried medical conditions, prescription and nonprescription medication use, social habits, dietary patterns, and physical activity. Creation of multiple cohort studies that evaluated risk factors for a wide range of diseases, including cancer, heart disease, and fractures. The British Doctors Study cohort was established in 1951 and followed for more than 50 years, although many of the original 40,701 participants are now dead. It has been of enormous value, particularly in relation to identifying the manifold health consequences of smoking. This is despite the fact that, compared with studies today, only limited exposure data were collected on a very short postal questionnaire mailed to the doctors at 10-year intervals since 1951 (Doll and Hill, 1964). The US Nurses’ Health Study started in 1976 with 121,964 female nurses aged 30–55, and 5 years of funding. Since then its focus has widened enormously from the oral contraceptive–breast cancer links for which it was first funded (Stampfer et al., 1988) to cover many exposures (including diet) and a multitude of outcomes. It has now accumulated more than 30 years of follow-up and is still going strong. It is very expensive to run, but the scientific and public health yield has been exceptional. The Nurses’ Health Study II began in 1989 with 117,000 nurses aged 25–42 (Rockhill et al., 1998) and recruitment has recently started for a Nurses’ Health Study III!
  • It is now generally accepted that studies on humans should be carried out with informed consent. This principle, originally developed in relation to controlled clinical trials, has generally now been extended to observational epidemiology studies, including cohort studies. In the past, if a cohort was recruited that involved the subjects participation in providing data, their agreement to supply the data (e.g. respond to a questionnaire) was generally regarded as implied consent. However, now, in addition to providing information on questionnaires, for many cohorts, biological specimens (e.g. blood, buccal cells) are requested, and then it becomes mandatory that the respondent provide consent for the future use of such specimens for research purposes. However, at the time the specimens are provided, it is impossible to know the precise use the investigators may wish to apply to this material. An example relates to the fact that the majority of participants in the sub-cohorts of the European Prospective Investigation of Diet and Cancer (EPIC; Riboli and Kaaks 1997) provided blood specimens in the early 1990s; a few without signing a consent form, the majority did so. However, now that genetic studies are commonplace on such specimens, it has become apparent that some of the consent forms did not specifically mention genetic analyses as potential research usages. This has led to difficulties in obtaining approval for such sub-studies from human experimentation committees, some of which wanted new consent forms to be signed, specific to the genetically-associated sub-study planned. Obtaining new consent, however, will become increasingly difficult as time goes on, and a number of subjects with the endpoint of interest may have died. In the United States, potential restrictions upon studies such as these have caused difficulties. In Europe, especially Scandinavia, there has been a more relaxed view of the ethical acceptability of studies on stored specimens, many such collections having been originally made without a formal informed consent process, but for which studies conducted with full preservation of confidentiality have been deemed to be ethically acceptable.
  • Intention to treat analysis : The conventional approach is to analyze the data in a intention-to treat fashion; that is, subjects are analyzed in the group to which they were originally assigned, regardless of what occurred after that point. Given that it reduces observed risk, however, some researchers choose to additionally analyze in a “ treatment-as-received ” manner. A number of statistical methods, including Cox proportional hazard modeling and Poisson regression, are suitable for this approach. In the latter technique, rather than allowing a single subject to remain in only one group for analysis, the amount of “ person time ” each subject represents within a study is considered. If the groups being compared consist of a given treatment versus no treatment or an alternate therapy, it is possible that some controls will start treatment or subjects may switch therapies.
  • , such as using only one size blood pressure cuff to take measurements on both adults and children
  • Previous reports from the Registrar General had drawn attention to the possibility that differences in water supply were associated with differences in cholera rates across sections of London.
  • Previous reports from the Registrar General had drawn attention to the possibility that differences in water supply were associated with differences in cholera rates across sections of London.

Cohort Study Cohort Study Presentation Transcript

  • Cohort StudyPrepared by:Achyut Raj Pandey (Roll No. 61)MPH,2012SPH and CM, BPKIHS1
  • Concept of cohortThe word cohort is derived from the Latin “cohorts”meaning an enclosure, company, or crowd.In Roman times a cohort was a body of 300–600infantry.In epidemiological terms the cohort is a group ofpeople with something in common, usually anexposure or involvement in a defined populationgroup.2
  • Definition• Cohort study is a type of analytical studywhich is undertaken to obtain additionalevidence to refute or support existence ofassociation between suspected cause anddiseases.• Other names of cohort study are Longitudinalstudy, Incidence study and forward lookingstudy3
  • Features of cohort studies• Cohorts are identified prior to appearance ofdisease under investigation• The study groups are observed over a periodof time to determine the frequency of diseaseamong them• The study proceeds from cause to effects4
  • Indications for cohort study• There is good evidence of an association betweenexposure and disease, from other studies.• Exposure is rare.• Attrition of study population can be minimized.• Sufficient fund is available.5
  • Framework of cohort study6
  • Design of Cohort StudyThen(a+b) is called study cohort and (c+d) is called control cohort7
  • Consideration during selection ofCohort• The cohort must be free from disease under study.• Insofar as the knowledge permits, both the groupsshould be equally susceptible to disease under study.• Both the groups must be comparable in respect of allvariable which influence the occurrence of disease• Diagnostic and eligibility criteria of the disease mustbe defined beforehand. 8
  • Types of cohort study• Prospective study• Retrospective cohort study• Ambi-directional cohort study9
  • Prospective cohort study• The common strategy of cohort studies is to startwith a reference population (or a representativesample thereof), some of whom have certaincharacteristics or attributes relevant to the study(exposed group), with others who do not have thosecharacteristics (unexposed group).• Both groups should, at the outset of the study, befree from the condition under consideration. Bothgroups are then observed over a specified period tofind out the risk each group has of developing thecondition(s) of interest.10
  • Example of Prospective Cohort StudyFramingham Heart Study Framework• Initiated in 1948 to study therelationship of a variety of factorsto the subsequent development ofheart disease with 5127samples( 30 to 59 yrs ) atFramingham.• Study subjects were examinedevery 2 yrs for 20 years.• Daily Surveillance ofhospitalization at Framinghamhospital.• Study found that Hypertensive,tobacco smoking, elevated bloodcholesterol are associated to CHD• Increased physical activityassociated with decreased risk ofCHD11
  • Problem of prospective study• Study might take long duration.• Sufficient amount of funding for long period.• Missing of study subjects.12
  • Retrospective Cohort Study• A retrospective cohort study is one in which theoutcome have all occurred before the start ofinvestigation.• Investigator goes back to the past to select studygroup from existing records of the pastemployment, medical and other records andtraces them forward through time from the pastdate fixed on the records usually to the present.• Known with the name of Historical Cohort andnoncurrent cohort13
  • Example of Retrospective Study• Suppose that we began ourstudy on association betweensmoking habit and lung cancerin 2008• Now we find that an old rosterof elementary schoolchildrenfrom 1988 is available in ourcommunity, and that they hadbeen surveyed regarding theirsmoking habits in 1998.• Using these data resources in2008, we can begin todetermine who in thispopulation has developed lungcancer and who has not.14
  • Ambi-directional cohort Study• Elements of prospective and retrospectivecohort are combined.• The Cohort is identified from past records andassesses of date for the outcome. The samecohort is the followed up prospectively intofuture for the further assessment of outcome15
  • Example of Ambi-directional cohortstudy• Curt- Brown and Dolls study on effects ofradiation Began in 1955 with 13,352 patientswho received large dose of radiation therapy forankylosing spondylitis between 1934 to1954.• Outcome evaluated was death from Leukemia oraplastic anemia between 1934 to 1954.• A prospective component was added up in 1955and surviving subjects were followed up toidentify deaths in subsequent years16
  • Comparison of retrospective and prospectivecohort study17
  • Prognostic cohort studiesPrognostic cohort studies are a special type of cohort study usedto identify factors that might influence the prognosis after adiagnosis or treatment.These follow-up studies have the following features:The cohort consists of cases diagnosed at a fixed time, or casestreated at a fixed time by a medical or surgical treatment,rehabilitation procedure, psychological adjustment.By definition, such cases are not free of a specified disease, as inthe case of a conventional cohortThe outcome of interest is usually survival, cure, improvement,disability, or repeat episode of the illness, etc.18
  • Steps of Cohort Study19
  • 1. Selection of study subjectsThe usual procedure is to locate or identify the cohort,which may be a total population in an area or samplethereof. Cohort can be:• community cohort of specific age and sex;• exposure cohort e.g. radiologists, smokers, users oforal contraceptives;• birth cohort e.g. school entrants;• occupational cohort e.g. miners, military personnel;• marriage cohort;• diagnosed or treated cohort, e.g. cases treated withradiotherapy, surgery, hormonal treatment.20
  • Open or dynamic cohort• Open population or dynamic population describe apopulation in which the person-time experience canaccrue from a changing roster of individuals.• For example, in a study, the incidence rates ofcancer reported by the Connecticut Cancer Registrycome from the experience of an open population.Because the population of residents of Connecticutis always changing, the individuals who contributeto these rates are not a specific set of people whoare followed through time.21
  • Fixed and Closed Cohort• Fixed Cohort :When the exposure groups in acohort study are defined at the start of follow-up,with no movement of individuals betweenexposure groups during the follow-up, the groupsare called fixed cohorts.• If no losses occur from a fixed cohort, the cohortsatisfies the definition of a closed population andis often called a closed cohort22
  • 2. Obtaining data on Exposure• From Cohort Members : Personal interview,mailed questionnaire• Review of Records : Certain kinds of informationlike dose of radiation, kinds of surgery receivedcan only be obtained from medical records.• Medical examination/ Special tests: In somecases information needs to be obtained frommedical examination like in case of bloodpressure, serum cholesterol,• Environmental Survey of location where cohortlives23
  • Information should be collected in a mannerthat allows classification of cohort accordingto• whether or not they have been exposed tosuspected factor• According to level or degree of exposure• Demographic variables which might influencefrequency of disease under investigation24
  • 3. Comparison GroupInternal ComparisonGroup :Single Cohort enters thestudy and its members onthe basis of informationobtained , can beclassified into severalcomparison according todegree of exposureClassificationof exposureNo. ofDeathsDeath rate½ pack 24 95.2½ to 1 pack 84 107.821-2 pack 90 229.2+ 2 pack 97 264.2Age Standardized death rate among100000 men per year according toamount of cigarette smoking25
  • External Comparison Group: when information ondegree of exposure is not available.if all workers at the factory had some degree ofexposure, we would need to select a comparisongroup from another population, possibly anothertype of factoryComparison with general population can also beused as comparison group26
  • 4. Follow UP• The length of follow-up that is needed forsome studies to reach a satisfactory end-point, when a large enough proportion of theparticipants have reached an outcome, maybe many years or even decades.• At the start of study, method should bedetermined depending on the outcome ofstudy to obtain data for assessing outcome.27
  • Procedure may be:• Periodic medical examination of each memberof cohort• Reviewing physician and hospital records• Routine surveillance of death records• Mailed questionnaire, telephone calls andperiodic home visits28
  • 5. AnalysisData analyzed in terms of• Incidence rate of outcome among exposedand non exposed• Estimation of risk29
  • Incidence rateChoice between cumulative incidence and Incidence Densityis a crucial issue• Cumulative incidence: In cohort studies on acute diseaseswith short induction periods and a short time of follow-up,like outbreaks, the risk of disease can be estimated directlyusing the cumulative incidence, given a fixed cohort withfixed period of follow-up and a low fraction of drop-outs.• Incidence Density: In cohort studies on chronic diseaseswith their long follow-up periods, however, the use of thecumulative incidence is not appropriate because usuallydisease-free follow-up periods differ strongly amongcohort members. In such case incidence density is appositemeasure 30
  • Death No death IncidencerateTotalExposed A B A/(A+B) A + BUnexposedC D C/(C+D) C + DTotal A + C B + D A+B+C+DOutcome** Outcome : death/diseaseANALYSIS OF COHORT STUDIES31
  • A = Exposed persons who later develop disease or dieB = Exposed persons who do not develop diseases or dieC = Unexposed persons who later develop disease or dieD = Unexposed persons who do not develop diseases or dieThe total number of exposed persons = A + BThe total number of unexposed persons = C + DIncidence of disease(or death) among exposed= A/A+BIncidence of disease(or death) among non-exposed= C/C+D32
  • Relative Risk (RR)• Estimates the magnitude of an association between exposureand disease• Indicates the likelihood of developing the disease in theexposed group relative to those who are not exposed• Ratio of risk of disease in exposed to the risk of disease innonexposedRelative RiskRR =Risk in exposed(Incidence in exposed group)Risk in non exposed(Incidence in non exposed group)33
  • EXAMPLE34
  • Children(<12 yrs)1000Familysmoker500 childrenExposedFamily non-smoker500 childrenNot exposedDiseased300Not diseased200Diseased120Not diseased380OutcomeStart35
  • Rate: Incidence rate•Incidence of Resp. Infection among exposedchildren: 300500 = 60%•Incidence of Resp. Infect. Among non exposedchildren: 120500 = 24%36
  • Cohort Study (cont.)Relative Risk: Incidence rate among exposedRisk Ratio Incidence rate in non exposed.6024 = 2.5Exposed individuals are 2.5 times more likely todevelop disease than non exposed individuals.37
  • Difference Measures• Attributable risk– No. of cases among the exposed that could be eliminatedif the exposure were removed= Incidence in exposed - Incidence in unexposed• Population Attributable Risk percentage:PAR expressed as a percentage of total riskin population100xII-IPAR%populationunexposedpopulation=38
  • Attributable RiskIncidenceExposed UnexposedIexposed – IunexposedI = Incidence39
  • Yes No Incidence RDYes 100 1900 2000 0.05No 80 7920 8000 0.01180 9820 10000AR: Smoking and Lung cancerSmoking0.04Lung CancerAttributable risk = Incidence in exposed - Incidence in unexposed=0.5-0.1=0.440
  • • Excess risk of disease in total populationattributable to exposure• Reduction in risk which would be achieved ifpopulation entirely unexposed• Helps determining which exposures relevantto public health in communityPopulation Attributable Risk (PAR)unexposedpopulation I-IPAR =41
  • Population Attributable RiskRiskPopulation Unexposedunexposedpopulation I-IIpopln– Iunexposed42
  • Yes No RiskYes 100 1900 2000 Incidence in exposed= 0.050No 80 7920 8000 Incidence in unexposed=0.010180 9820 10000 Incidence in population=0.018PAR: Smoking44%100x0.0180.010-0.018PAR% ==0.0080.010-0.018PAR ==SmokingLung Cancer43
  • Conclusion:44% of lung cancer in the population could beprevented if use of smoking were eliminated44
  • But calculationsarenot that simple in real Cohort studies45
  • British Doctors Study• In 1951, a prospective cohort study was set up among Britishdoctors to investigate the relationship between smoking andmortality, particularly the association between smoking and lungcancer• In 1951, a questionnaire on smoking habits was sent to 49,913 maleand 10,323 female doctors , 34,440 male doctors and 6194 femaledoctors gave sufficient information to classify their smoking status.• The causes of death of 10,072 male and 1094 female doctors whohad died during this period were ascertained from deathcertificates.• The rate of death from lung cancer among smokers was comparedto that among non-smokers.46
  • 47
  • Since mortality depends on age and the distribution of subjects by age groupis different between the smokers and non-smokers, the effect of age onmortality has to be adjusted for when making comparison on lung cancermortality between these two groups. A commonly used method to adjust forthe age is direct standardization48
  • It would not be rational to categorize individualsmoking one cigarette per day and more than 25cigarette in same category with equal emphasisSoIts better we opt for stratification49
  • Again its not only the dose of exposure that determines the frequency ofdisease, there are some other factors like duration of exposure and age atinitiation of exposure that can influence occurrence of disease. We need tomake adjustment for that too50
  • The relative risk of lung cancer death increased with the level of smoking inboth males and females. The relative risk in the men smoking 1–14 and 15–24 cigarettes per day is much higher than in the women; in the groupsmoking 25 or more cigarettes per day, the relative risk in men is marginallyless than that in women. Does this mean that the effect of low levels ofsmoking is higher among men than among women?51
  • The proportion of men inhaling smoke is higher than women in all three levels ofsmoking. Men seemed to have started to smoke at an earlier age than women.Since these features of smoking may modify the effect of smoking on lung cancer,their effects have to be adjusted for when comparing the association betweensmoking and lung cancer in men and women.52
  • …….. too complicated ????ButProblem does not end here….53
  • What if, a subject is followed up from age 23 but has been exposed from age 19on, he|she is exposed until age 27 followed by an unexposed 5 year period. He|she isagain exposed until age 39 at which time his|her person-time at risk ceases eitherbecause of disease diagnosis or because of end of follow-up.54
  • For analyzing such data we use Poisson modelsand Cox Proportional HazardsSpecialized software packages exist to performthese computations such as Stata (Version 7or later and Epicure55
  • Advantage of Cohort Studies• Temporality can be established• Incidence ca be calculated.• Several possible outcome related to exposurecan be studied simultaneously.• Provide direct estimate of risk.• Since comparison groups are formed beforedisease develops certain forms of bias can beminimized like misclassification bias.• Allows the conclusion of cause effectrelationship 56
  • Disadvantage of Cohort Studies• Large population is needed• Not suitable for rare diseases.• It is time consuming and expensive• Certain administrative problems like loss of staff,loss of funding and extensive record keeping arecommon.• Problem of attrition of initial cohort is common• Study itself may alter people’s behavior57
  • Ethics in Cohort Study• Classic example issues on research ethics isTuskegee study on natural history of syphilis inwhich US Public health service recruited 399 poorblack sharecroppers in Macon County as cohort.• Study was lasted from 1932 to 1972.• They were denied of treatment of syphilisalthough effective treatment was available.Government deceived by saying that they werebeing treated.58
  • Ethics in Cohort Study• On July 26, 1972, The New York Times describedthe study as “the longest non therapeuticexperiment on human beings in medical history.”The disclosure of this study by the press was amajor scandal in the United States.• Led to The Belmont Report: Ethical Principles andGuidelines for the Protection of Human Subjects inResearch59
  • Ethics in Cohort Study• These problems can be encountered in cohortstudy designed to study natural history of disease.• What if treatment becomes available in themiddle of research, should we continue researchwith treatment denial of abort research?• Should we communicate the research finding toindividuals are controversial issues.60
  • Biases in cohort studyDifferential loss of follow upDifferential follow-up between compared groupsmay be a major problem. Losses to follow-up,whether due to study withdrawals, unmeasuredoutcomes, or unknown reasons, are always aconcern.This is particularly true when more outcome data ismissing in one group than another, as there is noway to be certain that the factor being studied isnot somehow related to this observation.61
  • ContaminationSubjects initially unexposed to the risk factor ofinterest may become exposed at a later date.Such “ contamination ” tends to reduce theobserved effect of the risk factor.62
  • Selection BiasPerhaps the largest threat to the internal validity of acohort studies is selection bias, also called case-mixbias .Select participants into exposed and not exposed groupsbased on some characteristics that may affect theoutcomeInformation bias−Collect different quality and extent of information fromexposed and not exposed groups63
  • Misclassification BiasDifferential misclassificationNon differential misclassification64
  • • Differential misclassification – Errors inmeasurement are one way only– Example: Measurement bias – instrumentation maybe inaccurate, same cut off level of weight for maleand female to determine malnourishment65
  • Misclassification Bias (cont.)2501001501005050Nonexposed15050100ExposedTotalDisease-Disease +RR = a/(a+b)/c/(c+d) = 1.3True Classification250100150905040Nonexposed16050110ExposedTotalDisease -Disease +RR = a/(a+b)/c/(c+d) = 1.6Differential misclassification - Overestimate exposurefor 10 cases, inflate rates66
  • • Nondifferential (random) misclassification –errors in assignment of group happens in more thanone direction– This will dilute the study findings -BIAS TOWARD THE NULL67
  • Misclassification Bias (cont.)Disease + Disease - TotalExposed 100 50 150Nonexposed 50 50 100150 100 250RR = a/(a+b)/c/(c+d) = 1.3True ClassificationDisease + Disease - TotalExposed 110 60 170Nonexposed 40 40 80150 100 250RR = a/(a+b)/c/(c+d) = 1.3Nondifferential misclassification - Overestimateexposure in 10 cases, 10 controls – bias towards null68
  • Control of Bias• Restriction• Stratification• Mathematical Modeling-Poisson regression model-Cox proportional hazard69
  • When Is a Cohort Study Warranted?• When the (alleged) exposure is known• When exposure is rare and incidence of diseaseamong exposed is high (even if the exposure israre, determined investigators will identifyexposed individuals)• When the time between exposure and disease isrelatively short• When adequate funding is available• When the investigator has a long life expectancy70
  • Reference• Park.k.,(2007), Park’s textbook of preventive andsocial medicine(19thedition)• Gordis.L.,(2008), Epidemiology.,(4thedition)• Framimgham Heart study retrived fromwww.framingham.com/heart/timeline.htm,on 29thJan,2011.71
  • THANK YOU72
  • Classic example of Cohort study :Study on London Cholera Outbreak• The classical study on the London choleraepidemic of 1849 conducted by John Snow is anexample of a cohort study on infectious diseases .• Two different water companies (the Lambeth andthe Southwark & Vauxhall) supplied householdswithin various regions of London73
  • Classic example of Cohort study :Study on London Cholera Outbreak• The companies differed in one important feature, thelocation of the water intake. The Lambeth had moved theirwater intake upstream from the sewage discharge point in1849; whereas, the Southwark & Vauxhall continued toobtain water downstream of the sewage discharge point.• Dr. Snow classified households according to their exposureto the two water sources and showed a substantialdifference in cholera mortality, 315 versus 37 choleradeaths per 10,000 households served by the Lambeth andSouthwark & Vauxhall companies, respectively.74
  • Summary of analysis75